Simultaneous quantitation of pioglitazone and its metabolites in human serum by liquid chromatography and solid phase extraction

Zhong, Wei-Zhu; Williams, Marta G.

doi:10.1016/0731-7085(95)01665-1

Cited by 50 publications

(22 citation statements)

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“…Pioglitazone and rosiglitazone were dissolved in dimethyl sulfoxide (DMSO) at stock concentrations of 10 mM; final concentrations used for treatment were in the range of 2.5 to 10 M for both drugs. Reported mean effective serum concentrations for the treatment of T2DM patients are 1 M for rosiglitazone (Cox et al, 2000) and 2.5 M for pioglitazone (Zhong and Williams, 1996). 8Br-cAMP was diluted in phosphate-buffered saline at a concentration of 100 mM; final concentration for treatment was 0.5 mM.…”

Section: Methodsmentioning

confidence: 99%

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Pioglitazone Inhibits Androgen Production in NCI-H295R Cells by Regulating Gene Expression of CYP17 and HSD3B2

Kempná

Hofer²,

Mullis³

et al. 2006

Mol Pharmacol

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Thiazolidinediones (TZDs) such as pioglitazone and rosiglitazone are widely used as insulin sensitizers in the treatment of type 2 diabetes. In diabetic women with polycystic ovary syndrome, treatment with pioglitazone or rosiglitazone improves insulin resistance and hyperandrogenism, but the mechanism by which TZDs down-regulate androgen production is unknown. Androgens are synthesized in the human gonads as well as the adrenals. We studied the regulation of androgen production by analyzing the effect of pioglitazone and rosiglitazone on steroidogenesis in human adrenal NCI-H295R cells, an established in vitro model of steroidogenesis of the human adrenal cortex. Both TZDs changed the steroid profile of the NCI-H295R cells and inhibited the activities of P450c17 and 3␤HSDII, key enzymes of androgen biosynthesis. Pioglitazone but not rosiglitazone inhibited the expression of the CYP17 and HSD3B2 genes. Likewise, pioglitazone repressed basal and 8-bromo-cAMP-stimulated activities of CYP17 and HSD3B2 promoter reporters in NCI-H295R cells. However, pioglitazone did not change the activity of a cAMP-responsive luciferase reporter, indicating that it does not influence cAMP/protein kinase A/cAMP response element-binding protein pathway signaling. Although peroxisome proliferator-activated receptor ␥ (PPAR␥) is the nuclear receptor for TZDs, suppression of PPAR␥ by small interfering RNA technique did not alter the inhibitory effect of pioglitazone on CYP17 and HSD3B2 expression, suggesting that the action of pioglitazone is independent of PPAR␥. On the other hand, treatment of NCI-H295R cells with mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059) enhanced promoter activity and expression of CYP17. This effect was reversed by pioglitazone treatment, indicating that the MEK/ ERK signaling pathway plays a role in regulating androgen biosynthesis by pioglitazone.The gonads and the adrenals are the main sources of human androgens and express common genes for the biosynthesis of androgens. P450c17 and 3␤HSDII, encoded by the CYP17 and HSD3B2 genes, are key enzymes involved in biosynthesis of androgens. The mature adrenal cortex in humans produces androgens from cholesterol in a multistep pathway. In a first step, cholesterol is converted to pregnenolone by the P450 side-chain cleavage system. Second, pregnenolone then may be converted to 17␣-hydroxypregnenolone and to dehydroepiandrostenedione (DHEA) by the 17␣-hydroxylase and 17,20-lyase activities of P450c17. Third, DHEA is converted to androstenedione by 3␤-hydroxysteroid dehydrogenase type 2 (3␤HSDII). Although the fetal adrenals predominantly produce androgens, postnatal androgen production ceases only to resume at the age of 6 to 7 years, after the development of the zona reticularis, the third layer of the mature adrenal cortex.Thiazolidinediones (TZDs) are a class of oral insulin-sensitizing agents that are generally believed to exert their action as...

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Section: Methodsmentioning

confidence: 99%

“…Error bars are S.D. ; ‫,ء‬ p Ͻ 0.02. clinical setting of patients with T2DM (1-5 M) (Zhong and Williams, 1996). But direct comparison of effective drug concentrations in vivo and in vitro may be inappropriate for many reasons such as binding of the drug to proteins or accumulation in tissues.…”

Section: Downloaded Frommentioning

confidence: 99%

Pioglitazone Inhibits Androgen Production in NCI-H295R Cells by Regulating Gene Expression of CYP17 and HSD3B2

Kempná

Hofer²,

Mullis³

et al. 2006

Mol Pharmacol

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“…26 Serum pioglitazone concentrations in the LϩPio3 and LϩPio20 groups were 0.46Ϯ0.13 and 2.16Ϯ0.31 g/mL, respectively. The concentrations of pioglitazone achieved by 3 and 20 mg doses in rats were equivalent to the concentration reported in humans who were administered 15 and 30 mg doses of pioglitazone, respectively.…”

Section: Experimental Animalsmentioning

confidence: 99%

Antiinflammatory and Antiarteriosclerotic Effects of Pioglitazone

et al. 2002

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Abstract-Peroxisome proliferator-activated receptor-␥ (PPAR␥) ligands are widely used in patients with insulin resistance and diabetes. Because coronary artery disease is a major complication for such patients, it is important to determine the effects of PPAR␥ activation on arteriosclerosis. Long-term inhibition of endothelial NO synthesis by administration of N -nitro-L-arginine methyl ester (L-NAME) to rats induces coronary vascular inflammation (monocyte infiltration, monocyte chemoattractant protein-1 [MCP-1] expression) and subsequent arteriosclerosis. We examined the effects of pioglitazone (a PPAR␥ ligand) in this rat model to determine whether PPAR␥ activation with pioglitazone inhibits arteriosclerosis by its indirect effects on metabolic conditions or by direct effects on the cells participating to the pathogenesis of arteriosclerosis. We found that pioglitazone did not affect metabolic states, systolic blood pressure, or serum NO levels, but did prevent the L-NAME-induced coronary inflammation and arteriosclerosis. Pioglitazone did not reduce local expression of MCP-1 but markedly attenuated increased expression of the MCP-1 receptor C-C chemokine receptor 2 (CCR2) in lesional and circulating monocytes. PPAR␥ activation with pioglitazone prevented coronary arteriosclerosis, possibly by its antiinflammatory effects (downregulation of CCR2 in circulating monocytes).

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“…It improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis also improves glycemic control while reducing circulating insulin levels. Pioglitazone Determination of pioglitazone by various analytical methods like spectrophotometric method 2 and HPLC and MECK method 3 in tablet dosage form, HPLC and solid phase extraction method in human serum 4 and in dog serum 5 , HPLC and LC MS in human plasma 6,7 have been reported. But these methods are sophisticated, expensive and time consuming when compared to simple UV spectrophotometric method.…”

Section: Introductionmentioning

confidence: 99%

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2010

IJPSR

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UV spectrophotometric method was developed and validated for the analysis of pioglitazone in tablets. The analyses were performed in Phosphate buffer (pH 7.4). Beer's law was valid in concentration range of 10-50 mcg/ml and UV detection was done at 238 nm. The developed method was validated respect to linearity, precision, accuracy, selectivity / sensitivity applied to the determination of Pioglitazone in two pharmaceutical formulations. The obtained data from developed method was compared statistically. It was concluded that the developed method was suitable for the quality control of Pioglitazone in pharmaceuticals.

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Simultaneous quantitation of pioglitazone and its metabolites in human serum by liquid chromatography and solid phase extraction

Cited by 50 publications

References 3 publications

Pioglitazone Inhibits Androgen Production in NCI-H295R Cells by Regulating Gene Expression of CYP17 and HSD3B2

Pioglitazone Inhibits Androgen Production in NCI-H295R Cells by Regulating Gene Expression of CYP17 and HSD3B2

Antiinflammatory and Antiarteriosclerotic Effects of Pioglitazone

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